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Method for synthesizing aza-aryl-phenolic-ketone compound

A technology of heteroaryl phenol ketones and phenolic compounds, which is applied in the field of organic synthesis, can solve the problems of high price, low product selectivity, and difficulty in obtaining, and achieve high selectivity, wide applicability, and simple reaction operation Effect

Inactive Publication Date: 2016-06-08
HUNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these reactions are mostly multi-step reactions, and the selectivity of the product is low; or the substrate needs to be functionalized in advance. Relative harshness makes the reaction difficult to operate and increases the difficulty of obtaining the target product [References: BarrecaML, FerroS, RaoA, LucaLD, Zappala`M, MonforteAM, DebyserZ, WitvrouwM, ChimirriA.J.Med.Chem.2005,48,7084- 7088; LeeHY, ChangCY, LaiMJ, ChuangHY, KuoCC, ChangCY, ChangJY, LiouJP. Bioorg. Med. Chem. 2015, 23, 4230–4236; Spadaro, A. Frotscher, M. Hartmann, R. W. J. Med. Chem. 】

Method used

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  • Method for synthesizing aza-aryl-phenolic-ketone compound
  • Method for synthesizing aza-aryl-phenolic-ketone compound

Examples

Experimental program
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Effect test

Synthetic example 1

[0027] Synthesis of 2-hydroxy-3,5-dimethylphenol quinoline-2-methanone

[0028] Add 0.20 mmol 2-methylquinoline, 0.60 mmol 2,4-dimethylphenol, 0.06 mmol iodine, 0.20 mmol trifluoroacetic acid, 0.60 mmol DMSO, and 1.5 mL chlorobenzene solvent into the reactor. Under an oxygen atmosphere, heat to 120°C, keep stirring for 24 hours, stop the reaction, cool to room temperature, add saturated sodium carbonate solution to wash, extract with dichloromethane, dry, distill off the solvent under reduced pressure, and separate the crude product by column chromatography to obtain Target product, yield 68%. 1 HNMR (400MHz, CDCl 3 )δ12.50(s, 1H), 8.35(d, J=8.4Hz, 1H), 7.91(d, J=2.4Hz, 2H), 7.79-7.83(t, J=7.8Hz, 1H), 7.73( S, 1H), 7.65-7.69 (t, J=7.4Hz, 1H), 2.30 (s, 3H), 2.22 (s, 3H).

Synthetic example 2

[0030] Synthesis of 2-hydroxy-3,5-dimethylphenol-6-chloroquinoline-2-methanone

[0031] Add 0.20 mmol 6-chloro-2-methylquinoline, 0.60 mmol 2,4-dimethylphenol, 0.06 mmol iodine, 0.20 mmol trifluoroacetic acid, 0.60 mmol DMSO, and 1.5 mL chlorobenzene solvent into the reactor. Under an oxygen atmosphere, heat to 120°C, keep stirring for 24 hours, stop the reaction, cool to room temperature, add saturated sodium carbonate solution to wash, extract with dichloromethane, dry, distill off the solvent under reduced pressure, and separate the crude product by column chromatography to obtain Target product, yield 80%. 1 HNMR (400MHz, CDCl 3 )δ12.35(s,1H),8.27(d,J=8.4Hz,1H),8.16(d,J=9.2Hz,1H),7.90-7.93(m,2H),7.70-7.75(m,2H ), 7.24(s,1H), 2.30(s,3H), 2.22(s,3H).

Synthetic example 3

[0033] Synthesis of 2-Hydroxy-3,5-Dimethylphenol-6-fluoroquinoline-2-methanone

[0034]Add 0.20 mmol 6-fluoro-2-methylquinoline, 0.60 mmol 2,4-dimethylphenol, 0.06 mmol iodine, 0.20 mmol trifluoroacetic acid, 0.60 mmol DMSO, and 1.5 mL chlorobenzene solvent into the reactor. Under an oxygen atmosphere, heat to 120°C, keep stirring for 24 hours, stop the reaction, cool to room temperature, add saturated sodium carbonate solution to wash, extract with dichloromethane, dry, distill off the solvent under reduced pressure, and separate the crude product by column chromatography to obtain Target product, yield 70%. 1 HNMR (400MHz, CDCl 3 )δ12.38(s,1H),8.31(d,J=8.8Hz,1H),8.21-8.25(m,1H),7.94(d,J=8.8Hz,1H),7.73(s,1H), 7.52-7.59 (m, 2H), 7.25 (d, J=9.2Hz, 1H), 2.31 (s, 3H), 2.23 (s, 3H).

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Abstract

The invention provides a method for synthesizing an aza-aryl-phenolic-ketone compound. The method includes the steps that under the oxygen atmosphere or the nitrogen atmosphere or the air atmosphere, an iodine compound is used as a unique catalyst or a unique acid reagent or a unique cooperative oxidant or a unique reactive solvent, and the aza-aryl-phenolic-ketone compound is directly synthesized through a methyl-substituted aza-aromatic compound and a phenolic compound. According to the method, metal catalysts do not need to be led in, and ligand and special reaction conditions such as microwave radiation are not required. Substrates are low in cost and easy to obtain, and largely exist in the nature, pre-functionalization is avoided, adaptability is high, and experiment operation is simple. Meanwhile, the method has good chemoselectivity and good regioselectivity, and acylation of the phenolic compound can be efficiently achieved. The target compound has the potential application prospects in the medicine aspect and particularly has the potential application prospects in the anticancer-substance design, research, development and application aspects, the fluorescence detection and tracking analysis aspect and the like.

Description

【Technical field】 [0001] The invention relates to the field of organic synthesis, in particular to a method for synthesizing azaarylphenol ketone compounds. 【Background technique】 [0002] Azaarylphenol ketones are very important basic building blocks in organic synthesis and natural product synthesis, and can achieve a variety of functional groups. At the same time, it shows good applicability in the field of drug synthesis, and is an important module of a class of potential anticancer and antineoplastic drugs and highly active phosphate prodrugs. [0003] At present, there are very limited reports on the methods of synthesizing azaarylphenol ketones. The general synthetic route is to use ortho-halogenated phenolic compounds and azaaromatic aldehydes as substrates, pre-protect the phenolic hydroxyl group, and adopt normal Butyllithium leaves the halogen at -78°C and then couples with azaaromatic aldehydes, and finally dephenolizes the hydroxyl group under strong acidic con...

Claims

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Application Information

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IPC IPC(8): C07D215/14C07D215/18C07D215/20C07D215/48C07D241/42C07D277/64C07D263/56C07D217/04
CPCC07D215/14C07D215/18C07D215/20C07D215/48C07D217/04C07D241/42C07D263/56C07D277/64
Inventor 尹双凤刘敏陈铁桥周永波
Owner HUNAN UNIV
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